The biological activities recovered from cartilage tissue, namely from shark cartilage have already been described. The processes of obtention of cartilage extracts and the properties of the extracts themselves are disclosed in international publications WO 95/32722, WO 96123512 and WO 97/16197: the contents of each of which are incorporated herein by reference. The processes generally comprise the steps of: homogenizing and extracting shark cartilage until a mixture of cartilage particles of an average size of about 500 μm and a crude liquid extract are obtained, separating the particles from said crude liquid extract, and fractionating the crude liquid extract, so as to recover molecules having a molecular weight lower than about 500 KDa. These processes apply to the extraction of biological activities from any source of cartilage.
Shark cartilage liquid extracts have been tested in various assays and they comprise anti-angiogenic, anti-collagenolytic, direct anti-tumor proliferating, and anti-inflammatory activities.
These cartilage extracts are described as being efficient against tumors and nevertheless innocuous since no serious adverse effect directly related to their oral administration has been observed in treated animals and human patients. The shark cartilage liquid extract and any other cartilage extract having equivalent anti-tumor activities are all within the scope of this invention and will be referred to as “cartilage extracts.”
A large panel of therapeutic agents is known for treating cancer. Anti-neoplastics include, but are not limited to, those of the following TABLE 1;
TABLE 1Alkylating AgentsAlkyl SulphonatesbusulfanEthylene IminesthiotepaNitrogen Mustard Analogueschlorambucilcyclophosphamideestramustine sodium phosphateifosfamidemechlorethamine hydrochloridemelphalanNitrosoureascarmustinelomustinestreptozocinPlatinum-containing CompoundscarboplatincisplatinAntimetabolitesFolic Acid Analoguesmethotrexate sodiumPurine AnaloguescladribinemecraptopurinethioguaninePyrimidine AnaloguescytarabinefluorouracilUrea DeriviativeshydroxyureaCytotoxic AntiobioticsAnthracyclinesdaunorubicindoxorubicin hydrochlorideepirubicin hydrochlorideidarubicin hydrochlorideActinomycinsdactinomycinVarious Cytotoxic Antibioticsbleomycin sulfatemitomycinmitotanemitoxanthrone hydrochloridePlant Alkaloids and OtherEpipodphyllotoxinsNatural ProductsetoposideteniposideTaxanesdocetaxelpaclitaxelVinca Alkaloids and Analoguesvinblastine sulfatevincristine sulfatevindesine sulfatevinorelbine tartrateVarious Anti-Neoplasticsaltretamineamsacrine1-asparaginasedacarbazinefludarabine phosphateporfimer sodiumprocarbazine hydrochloridetretinoin (all-trans retinoic acid), systemicAnti-angiogenicsMarimastatSuraminTNP 470Thalidomide, andRadiotherapeutics
Most of these anti-neoplastics or anti-tumor agents have a low safety margin since they are highly toxic, e.g., they provide severe undesirable effects at effective dosages.
It is an accepted fact, in the medical field, that no anti-tumor therapy is perfect. Pharmacologists and oncologists always have to deal with a compromise between a maximally effective dose and the toxic side effects thereof. As a result, an effective dose of a neoplastic may be given in a sub-maximal dose to avoid too severe toxic side effects to any possible extent. So, avoidance of severe toxic side effects unfortunately often has the priority of concern over maximal efficacy.
The cartilage extracts that we already described (op. cit.) are active in vivo against tumor proliferation, which activity appears to be due to a combination of at least a direct anti-tumor activity, anti-collagenolytic, and anti-angiogenic activities. This extract has a well-proven anti-tumor activity and is devoid of toxic side effects. Since the current studies in the field aim at obtaining an anti-tumor therapy which would have close to 100% efficacy with close to 0% toxicity, it will be readily appreciated that anti-tumor compositions approaching these gold standards would be greatly welcome.
There is therefore a need for anti-neoplastic therapies combining high anti-tumor efficacy and low toxic side effects.